Hydrophobic residue substitutions enhance the stability and <i>in vivo</i> immunogenicity of respiratory syncytial virus fusion protein

In this study, we demonstrate that introducing four hydrophobic residue substitutions into the RSV F protein leads to the generation of a highly stable prefusion F trimer (pre-F-IFLP) with improved expression levels in cultured cells and superior stability compared to DS-Cav1, the first-generation prefusion F-stabilized RSV vaccine. Furthermore, pre-F-IFLP induced significantly higher neutralizing antibody responses than DS-Cav1 following both the first and second booster immunizations and conferred complete protection against RSV infection in a mouse model. These findings present an alternative approach for stabilizing the trimeric prefusion F protein, enhancing its expression, and significantly improving its protective efficacy for the prevention of RSV infection <i>in vivo</i>.

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Publication Details

Journal
Journal of Virology
Published
2025-05-28
DOI
https://doi.org/10.1128/jvi.00087-25
Citations
2
Primary Topic
Respiratory viral infections research
Type
article
Field-Weighted Citation Impact
2.71

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article

Hydrophobic residue substitutions enhance the stability and in vivo immunogenicity of respiratory syncytial virus fusion protein

Haixia Yang, Yueyue Li, Wen‐Cai Ye, Hwei-Ling Cheng et al.
2 citations
Journal of Virology
Respiratory viral infections research
2.71
article

Hydrophobic residue substitutions enhance the stability and in vivo immunogenicity of respiratory syncytial virus fusion protein

Haixia Yang, Yueyue Li, Wen‐Cai Ye, Hwei-Ling Cheng, Qiao‐Yun Song, Wentao Shen, Jialiao Cai, Ying Wang, Wei Tang, Yaolan Li, Haoyue Zhu, Yun Hu, M F Qiu
article en
2 citations

Abstract

In this study, we demonstrate that introducing four hydrophobic residue substitutions into the RSV F protein leads to the generation of a highly stable prefusion F trimer (pre-F-IFLP) with improved expression levels in cultured cells and superior stability compared to DS-Cav1, the first-generation prefusion F-stabilized RSV vaccine. Furthermore, pre-F-IFLP induced significantly higher neutralizing antibody responses than DS-Cav1 following both the first and second booster immunizations and conferred complete protection against RSV infection in a mouse model. These findings present an alternative approach for stabilizing the trimeric prefusion F protein, enhancing its expression, and significantly improving its protective efficacy for the prevention of RSV infection <i>in vivo</i>.

Journal of VirologyVol. 99(6)
Jinan University (CN)
National Natural Science Foundation of China, Natural Science Foundation of Guangdong Province, Fundamental Research Funds for the Central Universities, Basic and Applied Basic Research Foundation of Guangdong Province
Good health and well-being
Openalex Percentile: Top 10%
Respiratory viral infections research
2.71
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Hydrophobic residue substitutions enhance the stability and <i>in vivo</i> immunogenicity of respiratory syncytial virus fusion protein — Haixia Yang, Yueyue Li, et al. · Journal of Virology (2025) | TGRS Research Map | TGRS